The major objectives of the proposal are the development of rapid tests for urinary bladder carcinogens and the prevention of bladder cancer in man by use of protease inhibitors. The detection of bladder carcinogens will help us define environmental hazards in commercial dyes and the nature of the proximal carcinogens. We will continue to develop sensitive assays for aromatic amines using fluorescamine and o-phthalaldehyde which can fluorometrically detect picomole amounts. Known and suspected bladder carcinogens will be fed to monkeys, dogs and mice and their urines examined for initiation in mouse skin and for mutagenicity in E. coli, S. typhimurium and yeast. Some of the compounds to be tested are, 2-aminonaphthalene, benzidine, azo dyes, p-phenylenediamine, and N-(4-(5-nitro-2-furyl)-2-thiazolyl formamide (FANFT). We will attempt to prevent bladder cancer in rats fed FANFT by use of the protease inhibitor leupeptin and dexamethasone which will increase the endogenous urinary inhibitor. Other protease inhibitors will also be used. The bladders will be examined by scanning electron microscopy and computerized light microscopy which can detect early carcinogenic changes.